It has previously been demonstrated that through the analysis of plasma DNA of a pregnant woman carrying a fetus, the maternal haplotypes inherited by the fetus can be deduced using the process of relative haplotype dosage analysis (RHDO) (Lo et al. Sci Transl Med 2010; 2: 61ra91 and U.S. Pat. No. 8,467,976). The haplotype information for the pregnant woman can be used. The haplotype information can be obtained using family analysis or a method for the direct analysis of the haplotype (e.g. Fan et al. Nat Biotechnol 2011; 29: 51-57; Snyder et al. Nat Rev Genet 2015; 16: 344-358). SNPs that are heterozygous in the mother but homozygous in the father can be used for the RHDO analysis.
Such a use of specific SNPs can limit the loci that can be used, and therefore limit the amount of data and accuracy. Such use of specific SNPs may also limit the clinical utility of the method as DNA samples from additional family members may not be available, and methods for the direct analysis of haplotypes would add costs to the analysis.